Imiquimod and the imidazoquinolones: mechanism of action and therapeutic potential

被引:298
作者
Stanley, MA [1 ]
机构
[1] Univ Cambridge, Dept Pathol, Cambridge CB2 1QP, England
关键词
D O I
10.1046/j.1365-2230.2002.01151.x
中图分类号
R75 [皮肤病学与性病学];
学科分类号
100206 ;
摘要
A central development of the past decade has been in our understanding of the interactions between, and interdependence of, the innate and adaptive immune responses. Innate immunity recognizes 'danger' signals and activates adaptive immunity in a targeted, appropriate and effective response. Dendritic cells and macrophages have a central role in this process, and pharmacological agents that modulate the functions of these cells could have therapeutic value. The imidazoquinolone compounds, of which imiquimod, formulated as Aldara(TM), is the best characterized to date, are such molecules. Imiquimod and its homologues act by activating macrophages and other cells via binding to cell surface receptors, such as Toll receptor 7, thereby inducing secretion of pro-inflammatory cytokines, predominantly interferon (IFN)-alpha, tumour necrosis factor (TNF)-alpha and interleukin (IL)-12. This locally generated cytokine milieu biases towards a Th1 cell mediated immune response with the generation of cytotoxic effectors, and this has been exploited clinically in the treatment of viral infections (human papillomavirus, herpes simplex virus, molluscum contagiosum) and nonmelanoma skin cancer. Imiquimod has been shown to be significantly more effective than placebo in clearing genital warts, and mechanism of action studies indicate that this is related to the ability to generate proinflammatory cytokines and a Th1 response. Intra-epithelial neoplasms of cutaneous and mucosal surfaces are associated with human papillomavirus infection and there is some evidence that immune response modifiers may have therapeutic value for these lesions. Topical immunotherapy with immunomodulators shows potential for effective and patient-friendly treatment of cutaneous viral infections. These compounds also have adjuvant properties that could significantly enhance conventional vaccine strategies.
引用
收藏
页码:571 / 577
页数:7
相关论文
共 50 条
[1]   Porokeratosis of Mibelli: successful treatment with 5% imiquimod cream [J].
Agarwal, S ;
Berth-Jones, J .
BRITISH JOURNAL OF DERMATOLOGY, 2002, 146 (02) :338-339
[2]   Imiquimod: a novel treatment for lentigo maligna [J].
Ahmed, I ;
Berth-Jones, J .
BRITISH JOURNAL OF DERMATOLOGY, 2000, 143 (04) :843-845
[3]   Enhancement of the innate and cellular immune response in patients with genital warts treated with topical imiquimod cream 5% [J].
Arany, I ;
Tyring, SK ;
Stanley, MA ;
Tomai, MA ;
Miller, RL ;
Smith, MH ;
McDermott, DJ ;
Slade, HB .
ANTIVIRAL RESEARCH, 1999, 43 (01) :55-63
[4]   Dermal dendritic cells in anogenital warty lesions unresponsive to an immune-response modifier [J].
Arrese, JE ;
Paquet, P ;
Claessens, N ;
Piérard-Franchimont, C ;
Piérard, GE .
JOURNAL OF CUTANEOUS PATHOLOGY, 2001, 28 (03) :131-134
[5]  
Barba A R, 2001, Dermatol Online J, V7, P20
[6]   EFFECTS OF THE IMMUNOMODULATING AGENT R837 ON ACUTE AND LATENT HERPES-SIMPLEX VIRUS TYPE-2 INFECTIONS [J].
BERNSTEIN, DI ;
HARRISON, CJ .
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, 1989, 33 (09) :1511-1515
[7]   Therapeutic response of basal cell carcinoma to the immune response modifier imiquimod 5% cream [J].
Beutner, KR ;
Geisse, JK ;
Helman, D ;
Fox, TL ;
Ginkel, A ;
Owens, ML .
JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY, 1999, 41 (06) :1002-1007
[8]   Treatment of genital warts with an immune-response modifier (imiquimod) [J].
Beutner, KR ;
Spruance, SL ;
Hougham, AJ ;
Fox, TL ;
Owens, ML ;
Douglas, JM .
JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY, 1998, 38 (02) :230-239
[9]   Imiquimod, a patient-applied immune-response modifier for treatment of external genital warts [J].
Beutner, KR ;
Tyring, SK ;
Trofatter, KF ;
Douglas, JM ;
Spruance, S ;
Owens, ML ;
Fox, TL ;
Hougham, AJ ;
Schmitt, KA .
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, 1998, 42 (04) :789-794
[10]  
Brown CW, 2000, CUTIS, V65, P363